1, 25-(OH)<sub>2</sub>D<sub>3</sub>及LPS对2型糖尿病肾病尿毒症患者单核细胞维生素D受体表达的影响

杨孟雪; 甘华; 沈清; 陈丹燕; 汤为学; 杨梅

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1, 25-(OH)₂D₃及LPS对2型糖尿病肾病尿毒症患者单核细胞维生素D受体表达的影响

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- 1, 25-(OH)₂D₃及LPS对2型糖尿病肾病尿毒症患者单核细胞维生素D受体表达的影响
- Effect of 1,25-(OH)₂D₃ and LPS on expression of vitamin D receptor in human monocytes incubated with sera from type 2 diabetes patients and diabetic nephropathy patients with uremia
- 陆军军医大学学报 2011年33卷第16期页码：1731-1735
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  中图分类号： R587.1;R392.12;R977.24
- 纸质出版：2011
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杨孟雪,甘华,沈清,陈丹燕,汤为学,杨梅.1, 25-(OH)2D3及LPS对2型糖尿病肾病尿毒症患者单核细胞维生素D受体表达的影响[J].陆军军医大学学报(原第三军医大学学报),2011,33(16):1731-1735.

　Yang Mengxue,Gang Hua,Sheng Qing,Chen Danyan,Tang Weixue,Yang Mei.Effect of 1,25-(OH)2D3 and LPS on expression of vitamin D receptor in human monocytes incubated with sera from type 2 diabetes patients and diabetic nephropathy patients with uremia[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(16):1731-1735.
杨孟雪,甘华,沈清,陈丹燕,汤为学,杨梅.1, 25-(OH)2D3及LPS对2型糖尿病肾病尿毒症患者单核细胞维生素D受体表达的影响[J].陆军军医大学学报(原第三军医大学学报),2011,33(16):1731-1735. DOI：

　Yang Mengxue,Gang Hua,Sheng Qing,Chen Danyan,Tang Weixue,Yang Mei.Effect of 1,25-(OH)2D3 and LPS on expression of vitamin D receptor in human monocytes incubated with sera from type 2 diabetes patients and diabetic nephropathy patients with uremia[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(16):1731-1735. DOI：

摘要

目的探讨1，25-(OH)

及TLR4配体（脂多糖，LPS）对2型糖尿病（T2DM）和糖尿病肾病（diabetic nephropathy

DN）尿毒症患者血清干预的单核细胞维生素D受体（VDR）表达的影响，进一步探索1，25-(OH)

在T2DM和DN炎症性免疫反应中的作用。方法分离研究对象（健康对照组、T2DM组和DN尿毒症组）外周血血清，孵育THP-1单核细胞，然后于含或不含10

-7

mol/L的1，25-(OH)

培养液中培养48 h后，再用终浓度为1 μg／ml的 LPS干预24 h，收集单核细胞和培养上清。采用RT-PCR检测VDR mRNA表达，Western blot、免疫荧光检测THP-1单核细胞内VDR蛋白表达。ELISA法检测细胞培养上清IL-6和IL-10浓度。结果与正常对照组比较，在LPS的刺激下T2DM组和DN尿毒症组THP-1单核细胞内VDR mRNA水平下调[对照组（0.99±0.25）；T2DM组（0.65±0.24）；DN尿毒症组（0.62±0.27），P0.05

]

；DN尿毒症组THP-1单核细胞内VDR蛋白表达比正常对照组和T2DM组显著下调[对照组(0.48±0.05)；T2DM组(0.50±0.06)；DN尿毒症组(0.20±0.01）

P0.01

]

，且LPS增强以上患者血清孵育的THP-1单核细胞炎症细胞因子IL-6的分泌[对照组(15.13±1.61)；T2DM组(24.06±2.92)；DN尿毒症组(70.77±5.48）

P0.05

]

；而1，25-(OH)

可部分阻断上述作用。结论 LPS能下调T2DM和DN尿毒症患者单核细胞VDR mRNA和蛋白的表达，引起促炎和抗炎细胞因子失调。1，25-(OH)

可部分逆转LPS的作用，对T2DM和DN尿毒症可能具有一定的保护作用。

Abstract

Objective To investigate the effects of 1

25-(OH)

and TLR4 ligand lipopolysaccharide (LPS) on the expression of vitamin D receptor (VDR) in THP-1 monocytes incubated with the sera from type 2 diabetes mellitus (T2DM) patients and diabetic nephropathy (DN) patients with uremia

and to explore the role of 1

25-(OH)

in the inflammatory immune response of T2DM and DN. Methods Peripheral blood sera of the subjects in healthy control group

T2DM group

and DN uremia group were isolated. THP-1 monocytes were incubated with the sera separately

cultured in media with or without 10

-7

mol/L 1

25-(OH)

for 48 h

and treated with 1 μg/ml LPS for 24 h. The monocytes and culture supernatant were collected. The mRNA and protein expression of VDR in THP-1 monocytes was evaluated by RT-PCR as well as Western blotting and immunofluorescence assay. ELISA was used to measure the IL-6 and IL-10 contents in the culture supernatant. Results With LPS treatment

T2DM group and DN uremia group showed down-regulated VDR mRNA expression in THP-1 monocytes as compared with the healthy control group (healthy control group 0.99±0.25; T2DM group 0.65±0.24; DN uremia group 0.62±0.27; P0.05)

and DN uremia group showed significantly down-regulated VDR protein expression in THP-1 monocytes as compared with the healthy control group and T2DM group (healthy control group 0.48±0.05; T2DM group 0.50±0.06; DN uremia group 0.20±0.01; P0.01). LPS enhanced IL-6 secretion of THP-1 monocytes in the T2DM group and DN uremia group as compared with the healthy control group (healthy control group 15.13±1.61; T2DM group 24.06±2.92; DN uremia group 70.77±5.48; P0.05). The above effects of LPS were partially blocked by 1

25-(OH)

. Conclusion LPS can down-regulate the mRNA and protein expression of VDR in monocytes in T2DM patients and DN patients with uremia

and cause pro-inflammatory and anti-inflammatory cytokine disorder.

The effects of LPS can be partially reversed by 1

25-(OH)

indicating the protective effects of 1

25-(OH)

on T2DM patients and DN patients with uremia.

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1, 25-(OH)2D3及LPS对2型糖尿病肾病尿毒症患者单核细胞维生素D受体表达的影响

Effect of 1,25-(OH)2D3 and LPS on expression of vitamin D receptor in human monocytes incubated with sera from type 2 diabetes patients and diabetic nephropathy patients with uremia

DOI：

摘要

Abstract

关键词

Keywords

references

1, 25-(OH)₂D₃及LPS对2型糖尿病肾病尿毒症患者单核细胞维生素D受体表达的影响

Effect of 1,25-(OH)₂D₃ and LPS on expression of vitamin D receptor in human monocytes incubated with sera from type 2 diabetes patients and diabetic nephropathy patients with uremia